Barrios, VicenteChowen, Julie A.Martín Rivada, ÁlvaroGuerra-Cantera, SantiagoPozo-Román, JesúsYakar, ShoshanaRosenfeld, Ron G.Pérez Jurado, Luis AlbertoSuárez, JuanArgente, Jesús2022-01-182022-01-182021Barrios V, Chowen JA, Martín-Rivada Á, Guerra-Cantera S, Pozo J, Yakar S, Rosenfeld RG, Pérez-Jurado LA, Suárez J, Argente J. Pregnancy-associated plasma protein (PAPP)-A2 in physiology and disease. Cells. 2021;10(12):3576. DOI: 10.3390/cells101235762073-4409http://hdl.handle.net/10230/52248The growth hormone (GH)/insulin-like growth factor (IGF) axis plays fundamental roles during development, maturation, and aging. Members of this axis, composed of various ligands, receptors, and binding proteins, are regulated in a tissue- and time-specific manner that requires precise control that is not completely understood. Some of the most recent advances in understanding the implications of this axis in human growth are derived from the identifications of new mutations in the gene encoding the pregnancy-associated plasma protein PAPP-A2 protease that liberates IGFs from their carrier proteins in a selective manner to allow binding to the IGF receptor 1. The identification of three nonrelated families with mutations in the PAPP-A2 gene has shed light on how this protease affects human physiology. This review summarizes our understanding of the implications of PAPP-A2 in growth physiology, obtained from studies in genetically modified animal models and the PAPP-A2 deficient patients known to date.application/pdfeng© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).info:eu-repo/semantics/articlehttp://dx.doi.org/10.3390/cells10123576IGF1IGF2IGFBPsPAPP-APAPP-A2STC1STC2Growth hormone axisinfo:eu-repo/semantics/openAccess